Glucocorticoids are highly effective for the topical treatment of inflammatory skin diseases and are a widely used class of anti-inflammatory drugs. Their long-term use, however, is accompanied by severe and partially irreversible adverse effects with skin thinning being the most prominent. General skin thinning consists of a reduction in epidermal and dermal thickness, regression of the sebaceous glands, subcutaneous fat loss, and muscle-layer atrophy. These changes are typically observed following 2 to 3 weeks of moderate- to high-potency topical glucocorticoid use. A single application of a very potent topical glucocorticoid can cause an ultrasonographically detectable decrease in skin thickness that lasts up to 3 days. Even low-potency topical glucocorticoids can cause slight skin thinning that often reverses upon discontinuation of the drugs. The cutaneous effects of glucocorticoid treatment are due to suppression of the proliferation and the extracellular matrix (ECM) protein synthesis of kerationcytes and fibroblast. The intercellular lipid layers are also reduced by glucocorticoids caused by the decreased synthesis of epidermal lipids, like ceramides, cholesterol and fatty acids. Thereby the stratum corneum gets thinner, followed by an increased transepidermal water loss. The skin loses its barrier function, its tensile strength and elasticity caused by the water loss and the degraded extracellular matrix. There is therefore a long felt medical need to alleviate these severe and unpleasant properties of glucocorticoids during treatment of inflammatory skin diseases. Glucocorticoid administration on the eye may also result in alterations of the epithelial surface (similar to keratinocytes) and conjunctiva, leading to keratitis.